CATALYST Raises Red Flag on Hypercortisolism in Type 2 Diabetes, with Ralph DeFronzo, MD


Ralph DeFronzo, MD, discusses the results of the first phase of the CATALYST trial and how results should influence the care of patients with difficult-to-treat type 2 diabetes.

On the final day of the 84th American Diabetes Association Scientific Sessions, investigators from the CATALYST trial dropped a proverbial bombshell on the diabetes community, with the revelations related to the prevalence of hypercortisolism among patients with difficult-to-control type 2 diabetes brought forth from the first half of the phase 4 trial.1

“These results are significant as they highlight a previously underrecognized factor contributing to the barriers when it comes to managing type 2 diabetes,” said lead investigator John Buse, MD, PhD, from the University of North Carolina School of Medicine Diabetes Center and Translational and Clinical Sciences Institute.2 “By identifying hypercortisolism in these patients, we can target treatments more effectively and potentially improve their outcomes.”

A 2-part trial, CATALYST was launched by Corcept Therapeutics with the intent of estimating the true prevalence of hypercortisolism among this patient population as well as to assess the effects of mifepristone (Korlym) in the management of these patients. With this in mind, the first part of the trial sought to screen 1000 patients with difficult-to-control type 2 diabetes for hypercortisolism. In the second part of the trial, investigators hope to assess the effects of mifepristone by randomizing patients who are diagnosed with hypercortisolism in a 2:1 ratio to mifepristone or placebo therapy.1

Results from the first half of the trial suggested the prevalence of hypercortisolism among the 1055 patients with difficult-to-control type 2 diabetes screened in the trial was 24% (n=253 of 1055; 95% CI, 21.4 to 26.7). In comparison to those without hypercortisolism, those with hypercortisolism were older, more likely to be on non-Hispanic or Latino ethnicity, more likely to be enrolled based on hypertension or micro/macrovascular complications, be taking newer classes of antihyperglycemic medications, and have a greater overall medication burden.1

Patients with hypercortisolism were also more likely to have cardiovascular risk. Investigators pointed out there was a prevalence of 35.4% among those taking 3 or more antihypertensive medications Analysis of adrenal imaging abnormality among 203 patients revealed 34% of patients had an adrenal abnormality. Additionally, 23% with hypercortisolism had a unilateral adrenal adenoma and were considered possible candidates for surgery.1

Evidence of the paradigm-shifting nature of the results, during the symposium Ralph DeFronzo, MD, chief of the Diabetes Division at UT Health San Antonio and creator of the Ominous Octet, suggested it was time to add hypercortisolism as the ninth factor contributing to impaired sugar metabolism.

For more on the trial results, what it means for patients and providers managing difficult-to-control type 2 diabetes, and how these results could immediately impact care, we caught up with DeFronzo during our time on-site at ADA 2024.

Relevant disclosures for Dr. DeFronzo include Corcept Therapeutics, AstraZeneca, Novo Nordisk, Alynylam Pharmaceuticals, and others.


  1. Buse J. Prevalence of Hypercortisolism in Difficult-to-Control Type 2 Diabetes. Presented at: American Diabetes Association (ADA) 84th Scientific Sessions. June 21 - 24, 2024. Orlando, FL.
  2. American Diabetes Association. One in four patients with difficult-to-control type 2 diabetes experience high levels of cortisol. American Diabetes Association Newsroom. June 24, 2024. Accessed June 24, 2024.
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